The development of flow and batch calorimeters has continued during the past year to the point that mixing artifacts in the 2 ml batch cell have been reduced to plus or minus 40 microjoules. Modification of this unit to serve as a metabolic calorimeter for the study of cell reactions will be started in the coming year. Optical pH, PCO2, and pO2 probes will be installed so that a constant environment may be maintained while at the same time measuring the consumption or production of these substances by the metabolizing cells. This can then be correlated with the heat produced to determine the thermochemistry of various substrate reaction paths. We hope then to be able to study the inhibition of these paths by various drugs. The Flow microcalorimeter has been improved considerably in the last year. A new molded polypropylene flow cell has been developed and tested. Flow artifacts are less than 10 microjoules in the differential mode. 30 microjoule electrical signals can be detected with a signal to noise ratio of ten to one. Diamond coating of the polyprepylene flow cell has stopped water evaporation. This instrument will be used for the study of protein reactions both with small molecule substrates and with nucleic acids. In particular, the study of the specificity of polyamine t-RNA transferase is underway.